title: Effect of D-amino acid oxidase activator (DAOA; G72) on brain function during verbal fluency.
abstract: BACKGROUND
  The D-Amino acid oxidase activator (G72 or DAOA) is believed to play a key role in the regulation of central glutamatergic transmission which is seen to be altered in psychosis. It is thought to regulate D-amino acid oxidase (DAO), which metabolizes D-serine, a co-agonist of NMDA-type glutamate receptors and to be involved in dendritic arborization. Linkage, genetic association and expression studies have implicated the G72 gene in both schizophrenia and bipolar disorder.
  
  
  OBJECTIVE
  To examine the influence of G72 variation on brain function in the healthy population.
  
  
  METHODS
  Fifty healthy volunteers were assessed using functional magnetic resonance imaging while performing a verbal fluency task. Regional brain activation and task-dependent functional connectivity during word generation was compared between different rs746187 genotypes.
  
  
  RESULTS
  G72 rs746187 genotype had a significant effect on activation in the left postcentral and supramarginal gyri (FWE P < 0.05), and on the task-dependent functional coupling of this region with the retrosplenial cingulate gyrus (FWE P < 0.05).
  
  
  CONCLUSIONS
  Our results may reflect an effect of G72 on glutamatergic transmission, mediated by an influence on D-amino acid oxidase activity, on brain areas particularly relevant to the hypoglutamatergic model of psychosis.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK. diana.prata@kcl.ac.uk
authors.forename: Diana P
authors.initials: DP
authors.lastname: Prata
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Papagni
authors.forename: Andrea
authors.initials: A
authors.lastname: Mechelli
authors.forename: Cynthia H Y
authors.initials: CH
authors.lastname: Fu
authors.forename: Joseph
authors.initials: J
authors.lastname: Kambeitz
authors.forename: Marco
authors.initials: M
authors.lastname: Picchioni
authors.forename: Fergus
authors.initials: F
authors.lastname: Kane
authors.forename: Sridevi
authors.initials: S
authors.lastname: Kalidindi
authors.forename: Colm
authors.initials: C
authors.lastname: McDonald
authors.forename: Eugenia
authors.initials: E
authors.lastname: Kravariti
authors.forename: Timothea
authors.initials: T
authors.lastname: Toulopoulou
authors.forename: Elvira
authors.initials: E
authors.lastname: Bramon
authors.forename: Muriel
authors.initials: M
authors.lastname: Walshe
authors.forename: Robin
authors.initials: R
authors.lastname: Murray
authors.forename: David A
authors.initials: DA
authors.lastname: Collier
authors.forename: Philip K
authors.initials: PK
authors.lastname: McGuire
mesh_terms: D000328:Adult; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000502:physiology; D059906:Neuroimaging; D020641:Polymorphism, Single Nucleotide; D014705:Verbal Behavior / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018698:Glutamic Acid